Device and method for repetitive needleless injection

ABSTRACT

A device for repetitive needleless injection including a handheld unit having at least a cell fillable with a liquid, and a propulsion mechanism to apply a sequence of pressure pulses to the liquid to eject a micro-jet of the liquid from the cell via an orifice with a velocity that is sufficient to enable the micro-jet to penetrate into the surface; a reservoir that is connected to the cell by a conduit to enable the liquid to flow from the reservoir to the cell; a controller that is configured to operate the propulsion mechanism repeatedly; and a unidirectional valve to enable flow of the liquid from the reservoir to the cell and to prevent backflow. The propulsion mechanism includes an impulse generator configured to displace an actuation surface to generate the pulse; a plunger to transmit the pulse to the cell, and a restoration mechanism to retract the plunger.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a continuation application of U.S. patentapplication Ser. No. 15/509,222, which was a national phase applicationof PCT International Patent Application No. PCT/IL2016/050369, filed onApr. 7, 2016, which claimed the benefit of U.S. Provisional PatentApplication No. 62/159,285, filed on May 10, 2015, all of which areincorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to injection. More particularly, thepresent invention relates to a device and method for repetitiveneedleless injection.

BACKGROUND OF THE INVENTION

Drugs, vaccinations, and other medical materials that are to bedelivered to tissue that is covered by skin are typically injected usinga hypodermic needle. Similarly, tattoos and permanent makeup are alsotypically applied using needles that penetrate the skin surface.

Although the use of needles for transcutaneous or subsurface delivery iswell established, being very robust and reliable, there are somedisadvantages to the use of needles. For example, reuse of needles maybe a common practice in regions or circumstances where an adequatesupply of needles cannot be relied upon. Such reuse of a needle afterinadequate sterilization could lead to infection or spread of diseaseagents from person to person. Some people are frightened by the sight ofthe needle and by the realization that the needle is to penetrate theirskin. Insertion of the needle is an invasive procedure which could bepainful, cause bleeding, or otherwise traumatize tissue to some extent.In some cases, momentary inattention to an exposed needle may result inaccidental pricking of medical personnel or of bystanders, possiblyresulting in injury or infection.

Needleless transcutaneous or subsurface delivery may require a smalleramount of the delivered liquid than delivery via a needle. Reducing theamount of the delivered liquid may reduce the probability of skinirritation or an allergic reaction.

SUMMARY OF THE INVENTION

There is thus provided, in accordance with an embodiment of the presentinvention, a device for repetitive needleless injection of a liquid intoa surface, the device including: a handheld unit that includes at leasta cell that is fillable with the liquid, and a propulsion mechanismconfigured to apply a sequence of pressure pulses to the liquid, eachpulse of the sequence of pressure pulses to eject a micro-jet of theliquid from the cell via an orifice between the cell and the exterior ofthe handheld unit with a velocity that is sufficient to enable themicro-jet to penetrate into the surface; a reservoir that is connectedto the cell by a conduit to enable the liquid to flow from the reservoirto the cell to replace the liquid that is ejected in the micro-jet; anda controller that is configured to operate the propulsion mechanismrepeatedly so as to eject a sequence of the micro-jets.

Furthermore, in accordance with an embodiment of the present invention,the orifice is separated from the cell by a unidirectional valve that isconfigured to enable flow of the liquid from the cell to the orifice andto prevent inflow from the orifice to the cell.

Furthermore, in accordance with an embodiment of the present invention,the unidirectional valve includes a stopper that is separable from anaperture.

Furthermore, in accordance with an embodiment of the present invention,a connection of the conduit to the cell includes a unidirectional valveto enable the liquid to flow from the conduit to the cell and to preventbackflow of liquid from the cell to the conduit.

Furthermore, in accordance with an embodiment of the present invention,the propulsion mechanism includes an impulse generator configured todisplace an actuation surface to generate the pulse and a plungerconfigured to move linearly to transmit the pulse to the cell.

Furthermore, in accordance with an embodiment of the present invention,the impulse generator includes a piezoelectric crystal.

Furthermore, in accordance with an embodiment of the present invention,the impulse generator includes a mechanical amplifier.

Furthermore, in accordance with an embodiment of the present invention,the plunger is bonded to the actuation surface.

Furthermore, in accordance with an embodiment of the present invention,the plunger is provided with a retraction mechanism that is configuredto retract the plunger after application of the pulse by the actuationsurface.

Furthermore, in accordance with an embodiment of the present invention,the retraction mechanism includes a spring.

Furthermore, in accordance with an embodiment of the present invention,the impulse generator is configured to expand to compress a propulsionresilient element and to contract to enable expansion of the propulsionresilient element to distally propel the plunger.

Furthermore, in accordance with an embodiment of the present invention,the controller is configured to control operation of the propulsionmechanism so as to control one or both of an amplitude of the pulse anda rise time of the pulse.

Furthermore, in accordance with an embodiment of the present invention,the controller is configured to control the one or both of an amplitudeof the pulse and a rise time of the pulse in accordance with anindicated dose or penetration depth.

Furthermore, in accordance with an embodiment of the present invention,the controller is configured to control operation of the propulsionmechanism so as to control a repetition rate for generation of thepulses.

Furthermore, in accordance with an embodiment of the present invention,the reservoir includes a liquid level sensor to sense a level of theliquid in the reservoir and the controller is configured to stopoperation of the propulsion mechanism when the sensed liquid level isbelow a threshold level.

Furthermore, in accordance with an embodiment of the present invention,the reservoir and the conduit are enclosed within the handheld unit.

Furthermore, in accordance with an embodiment of the present invention,the reservoir occupies a space between the plunger and a wall of thehandheld unit.

Furthermore, in accordance with an embodiment of the present invention,the cell occupies a constricted neck at a distal end of the handheldunit.

Furthermore, in accordance with an embodiment of the present invention,the conduit is interior to the plunger.

There is further provided, in accordance with a embodiment of thepresent invention, a method for repetitive needleless injection of aliquid into a surface, the method including: placing a nozzle of ahandheld unit of a needleless injection device at the surface, thedevice including a cell that is filled with the liquid; and operating acontroller of the device to repeatedly cause a propulsion mechanism ofthe device to apply a sequence of pressure pulses to the liquid, eachpulse of the sequence of pressure pulses to eject a micro-jet of theliquid from the cell via an orifice in the nozzle with sufficientvelocity to enable the micro-jet to penetrate into the surface, theliquid that is ejected from cell in the micro-jet the being replaced viaa conduit from a reservoir.

BRIEF DESCRIPTION OF THE DRAWINGS

In order for the present invention, to be better understood and for itspractical applications to be appreciated, the following Figures areprovided and referenced hereafter. It should be noted that the Figuresare given as examples only and in no way limit the scope of theinvention. Like components are denoted by like reference numerals.

FIG. 1 schematically illustrates a repetitive needleless injectiondevice, in accordance with an embodiment of the present invention.

FIG. 2 schematically illustrates a controller of the repetitiveneedleless injection device shown in FIG. 1.

FIG. 3 is a schematic pulse profile graph showing displacement as afunction of time of a component during a pulse of a propulsion system ofa repetitive needleless injection device, in accordance with anembodiment of the present invention.

FIG. 4A schematically illustrates a compact repetitive needlelessinjection device, in accordance with an embodiment of the presentinvention.

FIG. 4B schematically illustrates a compact repetitive needlelessinjection device as in FIG. 4A with the addition of a unidirectionalvalve for impeding inflow of air.

FIG. 5A schematically illustrates a compact repetitive needlelessinjection device as in FIG. 4A with the addition of a retainingmechanism.

FIG. 5B schematically illustrates a compact repetitive needlelessinjection device as in FIG. 5A with the addition of a unidirectionalvalve for impeding inflow of air.

FIG. 6A schematically illustrates operation of a pair of unidirectionalvalves when no pressure is applied.

FIG. 6B schematically illustrates the unidirectional valves shown inFIG. 6A when a plunger rod is being pushed in the distal direction.

FIG. 6C schematically illustrates the unidirectional valves shown inFIG. 6B when the plunger rod has being pushed to its maximal extent.

FIG. 6D schematically illustrates the unidirectional valves shown inFIG. 6C when the plunger rod is being retracted in the proximaldirection.

FIG. 6E schematically illustrates the unidirectional valves shown inFIG. 6D when the plunger rod has been fully retracted.

FIG. 7A schematically illustrates an alternative propulsion mechanismfor the compact repetitive needleless injection device shown in FIG. 4A.

FIG. 7B schematically illustrates a plunger retraction phase ofoperation of the alternative propulsion mechanism shown in FIG. 7A.

FIG. 7C schematically illustrates an impulse generator contraction phaseof operation of the alternative propulsion mechanism shown in FIG. 7B.

FIG. 7D schematically illustrates a plunger extension phase of operationof the alternative propulsion mechanism shown in FIG. 7C.

FIG. 8 schematically illustrates a compact repetitive needlelessinjection device with a reservoir that is not coaxial with a propulsionsystem.

DETAILED DESCRIPTION OF THE INVENTION

In the following detailed description, numerous specific details are setforth in order to provide a thorough understanding of the invention.However, it will be understood by those of ordinary skill in the artthat the invention may be practiced without these specific details. Inother instances, well-known methods, procedures, components, modules,units and/or circuits have not been described in detail so as not toobscure the invention.

Although embodiments of the invention are not limited in this regard,discussions utilizing terms such as, for example, “processing,”“computing,” “calculating,” “determining,” “establishing”, “analyzing”,“checking”, or the like, may refer to operation(s) and/or process(es) ofa computer, a computing platform, a computing system, or otherelectronic computing device, that manipulates and/or transforms datarepresented as physical (e.g., electronic) quantities within thecomputer's registers and/or memories into other data similarlyrepresented as physical quantities within the computer's registersand/or memories or other information non-transitory storage medium(e.g., a memory) that may store instructions to perform operationsand/or processes. Although embodiments of the invention are not limitedin this regard, the terms “plurality” and “a plurality” as used hereinmay include, for example, “multiple” or “two or more”. The terms“plurality” or “a plurality” may be used throughout the specification todescribe two or more components, devices, elements, units, parameters,or the like. Unless explicitly stated, the method embodiments describedherein are not constrained to a particular order or sequence.Additionally, some of the described method embodiments or elementsthereof can occur or be performed simultaneously, at the same point intime, or concurrently. Unless otherwise indicated, the conjunction “or”as used herein is to be understood as inclusive (any or all of thestated options).

In accordance with an embodiment of the present invention, a repetitiveneedleless injection device is configured to repeatedly expel a sequenceof micro-jets of a liquid. The liquid may contain (e.g., as a solutionor suspension) a material that is to be introduced into the skin. Themicro-jets are expelled from a nozzle with sufficient force or velocitysuch that the expelled liquid may penetrate into skin to a requireddepth. The material, such as a pigment, dye, or medication, may thus bedelivered to a sufficient depth beneath the skin surface so as tofunction in an intended manner. For example, a dye may be injected to asufficient depth so as to permanently color the skin to form permanentmakeup or a tattoo. A medication may be injected to sufficient depth soas to be absorbed into the blood stream or otherwise effect an intendedtreatment.

A device that injects fluids into the skin without the use of needlethat penetrates the skin surface may be advantageous. A needlelessdevice may reduce or eliminate physical or psychological trauma, such asbleeding, that is sometimes associated with the use of hypodermicneedles. Needleless delivery may reduce or eliminate the risk ofinfection or injury that may sometimes accompany use of needles. In someapplications, use of a needleless device may enable safe reuse of theequipment, at least reducing some of the expense or complications (e.g.,ensuring timely delivery to remote locations, eliminating the expense ofneedle replacement and of special disposal of sharp objects, reductionof maintenance costs) that may be associated with the use of disposableneedles. Needleless delivery may enable achieving a desired result usingless liquid and in less time than would be required using a needle. Forexample, in cosmetic applications, such as application of permanentmakeup, the quantity of pigment may be less than with the use ofneedles.

Typically, a device that utilizes a needle cannot be safely moved attimes when the needle is inserted into the skin. As a result, a personwho manipulates a needle device may have to reposition the needle devicemanually for each application. For example, dots of pigment may beapplied to a bald area of a scalp to simulate hair. With a needle, theapplier would have to manually move the needle to each location where adot is to be applied. As a result, the dots may not be evenlydistributed over the scalp. On the other hand, a needless deliverydevice in accordance with an embodiment of the present invention may bemoved continuously during application of the dots. For example, askilled operator may be able to move the device at a constant speedduring application. As a result, the dots may be evenly distributed overthe scalp. Similar considerations may be relevant to other applicationsof delivery of a liquid substance to a skin surface.

A repetitive needleless injection device in accordance with anembodiment of the present invention includes a pressure cell. Apropulsion mechanism is configured to apply pulses of pressure to aliquid that fills the pressure cell. The pressure pulses may expelmicro-jets of the liquid via a dispenser nozzle of the cell. When thedispenser nozzle is placed against a skin surface, the expelledmicro-jet may penetrate into the skin. Thus, the liquid may beintroduced into the skin without the use of a needle.

For example, a propulsion mechanism may include an impulse generator anda plunger. The impulse generator is configured to generate the impulses.The plunger is configured to move linearly to transmit the impulses tothe cell to produce pressure pulses in the liquid in the cell. A distalend of the plunger may form a proximal wall of the pressure cell. (Asused with respect to the structure of the repetitive needlelessinjection device, the distal direction is the direction toward thedispenser nozzle. When the repetitive needleless injection device is inuse, the distal direction equivalently refers to a direction toward theskin surface into which the liquid is to be introduced. The proximaldirection refers to the direction toward the propulsion mechanism or,equivalently, toward a hand or holder that is holding or manipulatingthe repetitive needleless injection device when in use.)

When applying a pulse, the impulse generator may rapidly push theplunger in the distal direction. For example, an active surface of theimpulse generator may be displaced distally to push the plunger in thedistal direction. The plunger may thus rapidly increase the pressure ofthe liquid in the pressure cell sufficiently above atmospheric pressureso as to forcefully expel a micro-jet of the liquid out of the dispensernozzle.

After expulsion of the micro-jet, the active surface of the impulsegenerator may retract in the proximal direction. For example, thecoupling of the active surface with the plunger may be such that theretraction of the active surface retracts the plunger in the proximaldirection. As another example, a separate retraction or retentionmechanism may proximally retract the plunger when not forced to movedistally by action of the impulse generator. The retraction of theplunger may create suction within the pressure cell. As a result, liquidmay be drawn into the pressure cell from a reservoir of the liquid inorder to replace the volume of liquid that was expelled in themicro-jet.

The dispenser nozzle may be provided with a unidirectional valve thatenables expulsion of the micro-jet while preventing entry of gasses orother fluids from the ambient atmosphere. Thus when the plunger isretracted, the suction may draw liquid from the reservoir, rather thandrawing gasses from the ambient atmosphere inward via the nozzle.Alternatively or in addition, adhesive forces and surface tension at thenozzle may be sufficient to block entry of gasses via the nozzle duringretraction of the plunger.

For example, a unidirectional valve may include an aperture and astopper (e.g., in the form of a ball or having another form) on thedownstream side of the aperture. Downstream is used herein in relationto flow in a forward, allowed direction. When a forward flow of fluidflows through the aperture in the forward direction, the stopper may bepushed away from the aperture, enabling forward flow through theaperture. When a backward flow fluid flows in the opposite, backwarddirection, the stopper is pushed against the aperture, impeding orblocking flow through the aperture. A mechanism may be provided toreturn the stopper to the aperture after cessation of the forward flowor to prevent excessive separation between the aperture and the stopper.For example, a spring or other elastic element may be configured to pushor pull the stopper to the aperture. The stopper and aperture mayinclude a ferromagnetic material, with at least one of the stopper andaperture being magnetized.

The impulse generator may include a piezoelectric actuator, amagnetostrictive actuator, or similar actuator with a cycle time that isshort enough to enable a suitable repetition rate. As used herein, acycle time refers to the period of time from application of a pressurepulse until the repetitive needleless injection device and the impulsegenerator are ready to apply another pulse. Thus, the repetition rate isequal to the inverse of the cycle time. For example, if the cycle timeis about 1 millisecond, as is typical for a piezoelectric actuator, thenthe repetition rate may be up to about 1000 Hz.

A piezoelectric actuator may include a piezoelectric crystal that iscoupled to a mechanical amplifier. For example, a mechanical amplifiermay include an elliptical cell or a lever arrangement, as is known inthe art. The mechanical amplifier may be configured to convert a smalldisplacement of a surface of the piezoelectric crystal that is appliedto one part of the mechanical amplifier into a larger displacement thatis applied to the plunger. Similarly another type of actuator (e.g., aferromagnetic mass of a magnetostrictive actuator) may include amechanical amplifier. Another type of actuator may be used.

Components of a repetitive needleless injection device in accordancewith an embodiment of the present invention may be enclosed in ahandheld and manipulable casing. For example, the casing may be in theform of a pen or pistol with the dispenser nozzle at the distal end. Orexample, the handheld casing may enclose at least the dispenser nozzle,the pressure cell, the plunger, and the impulse generator.

The outer surface of the handheld casing may include one or morecontrols for user control of operation of the repetitive needlelessinjection device. Alternatively or in addition, some or all controls maybe mounted on a separate unit, such as a controller of the repetitiveneedleless injection device.

For example, the controls may include an activate control that may beoperated to start or stop operation of the impulse generator torepetitively expel micro-jets of liquid (e.g., a pushbutton or leverthat may be depressed to activate the impulse generator, and which maybe released to stop operation of the impulse generator). Operation of apower (e.g., on/off or off/standby) control may connect or disconnect anelectrical power supply (e.g., battery or connection to power mains,driver, or to other external power supply) to or from the repetitiveneedleless injection device (e.g., disconnecting the power supply in anoff state and connecting in an on or standby state). Other controls maybe operated to control operation of the repetitive needleless injectiondevice. For example, controls may be operated to control one or more ofa repetition rate of the impulse generator, a penetration depth (e.g.,determined at least in part by a speed of expulsion of the micro-jet, orby another property of the micro-jet or characteristic of operation ofthe impulse generator), a dose (e.g., determined at least in part by oneor more of the repetition rate, a micro-jet volume, or by otherparameters), or other characteristics of the injection of the liquidinto the skin.

In some cases, the handheld casing may enclose at least some componentsof a controller for controlling operation of the repetitive needlelessinjection device. Where components of the controller are external to thehandheld casing, the external controller components may be connected toone or more components within the handheld casing via a wired orwireless communications channel Some components of a power supply foroperation of electrically powered components of the repetitiveneedleless injection device (e.g., the impulse generator) may beenclosed within the handheld casing, or may be external to the handheldcasing.

A reservoir of liquid for replenishing the pressure cell after expulsionof a micro-jet may be external to the handheld casing. In this case thereservoir may be connected to the pressure cell via a flexible conduit.For example, the conduit may include flexible plastic tubing or otherflexible material, or include rigid tubes connected at flexible joints.One or more of a connection of the reservoir to the conduit, aconnection of the conduit to the pressure cell, or a point within theconduit may include a unidirectional valve. The unidirectional valve mayprevent liquid flow from the pressure cell to the conduit when theimpulse generator applies a pressure pulse to the pressure cell. Thus,the pressurized liquid may exit from the pressure cell only via thedispenser nozzle. On the other hand, the unidirectional valve may enableunimpeded flow of liquid from the reservoir and conduit and into thepressure cell when suction is applied to the pressure cell. Thus, theliquid in the pressure cell may be replenished from the reservoir afterexpulsion of a micro-jet.

Alternatively or in addition, the reservoir may be internal to thehandheld casing. For example, the reservoir may occupy a space betweenthe plunger and the outer walls of the handheld casing. In this case,the reservoir is located within the handheld casing proximal relative tothe pressure cell. The pressure cell may occupy a distal end of thehandheld casing (e.g., a constricted neck of the casing at a distal endof the handheld casing). A conduit may be incorporated within theplunger. At least An opening of the conduit may be open to thereservoir. Thus, liquid may flow from the reservoir via the conduit intothe pressure cell. On the other hand, when the plunger is pushed in thedistal direction to expel a micro-jet, a unidirectional valve at thedistal end of the conduit may prevent backflow of liquid from thepressure cell into the conduit.

FIG. 1 schematically illustrates a repetitive needleless injectiondevice, in accordance with an embodiment of the present invention. FIG.2 schematically illustrates a controller of the repetitive needlelessinjection device shown in FIG. 1.

Repetitive needleless injection device 10 includes handheld unit 12.Although components of repetitive needleless injection device 10 areshown in the schematic drawing as outside of handheld unit 12, at leastin some cases, those components may be enclosed within handheld unit 12.

Handheld unit 12 includes a casing that encloses components ofrepetitive needleless injection device 10 that are operable torepetitively eject a series of liquid micro-jets 30. Handheld unit 12may have the general form of an elongated cylinder. For example, theshape of handheld unit 12 may be similar to that of a pen, syringe,pistol barrel, or similar handheld or manipulable object. Whencomponents of repetitive needleless injection device 10 are not enclosedwithin handheld unit 12, handheld unit 12 may be connected to thoseexternal components via a suitable flexible connection. The flexibleconnection may be configured to enable sufficiently free manipulation ofhandheld unit 12 so as not to impede injection of material contained inliquid micro-jets 30 into the skin in a predetermined set ofapplications.

Handheld unit 12 encloses propulsion mechanism 13 and pressure cell 24.Propulsion mechanism 13 is configured to apply a series of pressurepulses to a liquid that fills pressure cell 24. As a result ofapplication of each pressure pulse, a liquid micro-jet 30 may be ejectedfrom pressure cell 24 via dispenser nozzle 26.

Propulsion mechanism 13 includes impulse generator 14 and plunger 16.Impulse generator 14 includes an actuator that is operable to produce animpulse (e.g., move a surface such as actuation surface 18 in a linearlyoutward direction). Plunger 16 is configured to be displaced linearly soas to transmit the impulse to pressure cell 24.

Plunger 16 is configured to move linearly back and forth within alongitudinal dimension of handheld unit 12, as indicated by pistonmotion arrow 22. Plunger 16 is configured to move in a distal direction(toward nozzle 26) in response to a displacement of actuation surface 18of impulse generator 14. Impulse generator 14 is configured to displaceactuation surface 18 in response to a driver signal that is generated byactuator driver 56 of controller 40 of repetitive needleless injectiondevice 10. Actuator driver 56 may generate driver signals with arepetition rate that is determined by operation of triggering oscillator54 of controller 40.

Actuator driver 56 may control operation of impulse generator 14 viaactuator connection 37. For example, actuator connection 37 may includean electric cable, e.g., a lightweight electric cable. In some cases,e.g., where handheld unit 12 includes a self-contained power supply,actuator connection 37 may include a wireless connection.

For example, impulse generator 14 may include a piezoelectric actuator,a magnetostrictive actuator, pulsed laser and a material that isconfigured to expand upon absorption of a laser pulse, an actuatedhigh-pressure vessel, a linear electromagnetic motor, a compressedmechanical spring, or another type of actuator that may be driven at asuitable repetition rate. A preference or requirement for a particularrepetition rate may be determined in accordance with an intendedapplication of repetitive needleless injection device 10. For example, arepetition rate may be selected so as to enable delivery of a sufficientamount of a material (e.g., a dye, medication, or other material) to theskin at a desired rate (e.g., during a comfortable or natural rate ofmovement of handheld unit 12 over the skin surface, or an otherwisedetermined rate).

An impulse generator 14 in the form of a piezoelectric actuator includesa piezoelectric crystal connected to suitable electrodes. The maximumdisplacement of a surface of the piezoelectric crystal may not besufficient to enable expulsion of a liquid micro-jet 30. In such a case,impulse generator 14 may include a mechanical amplifier. The mechanicalamplifier is configured to produce a sufficiently large displacement ofactuation surface 18 in response to a smaller displacement of a surfaceof the piezoelectric crystal that is applied to the mechanicalamplifier. For example, actuation surface 18 may represent a surface ofthe mechanical amplifier with amplified displacement, or a surface thatis mechanically coupled to such a surface of the mechanical amplifier.Similarly, an impulse generator 14 that includes a magnetostrictive orother type of actuator may include a mechanical amplifier.

For example, a mechanical amplifier may include an elliptical cell, anarrangement of one or more levers, or another type of mechanicalamplifier. For example, the amplification factor of the mechanicalamplifier may be about 10 (e.g., for a piezoelectric actuator), oranother suitable amplification factor.

Actuation surface 18 is configured to apply a force to proximal end 16 ato push plunger 16 in the distal direction. The force is transmitted toliquid in pressure cell 24 by distal end 16 b of plunger 16. Thus, theforce that is transmitted by plunger 16 may increase the pressure of theliquid in pressure cell 24 over the pressure that is applied by theambient atmosphere.

Pressure cell 24 may be configured such that the only outlet of liquidfrom pressure cell 24 under application of excess pressure is orifice 27of nozzle 26. For example, a diameter of distal end 16 b of plunger 16may be slightly less than the interior diameter of pressure cell 24. Anyspace between the perimeter of distal end 16 b and the interior walls ofpressure cell 24 may be filled with sealing structure (e.g., O-ring orother sealing structure). The sealing structure may include a lowfriction surface so as to prevent liquid flow between distal end 16 band walls of pressure cell 24 without unduly impeding motion of plunger16.

Structure of pressure cell 24 or of plunger 16 may be configured toprevent backflow of liquid from pressure cell 24 to reservoir 32 duringapplication of excess pressure to pressure cell 24. For example, aninlet conduit 34 for conducting the liquid from reservoir 32 to pressurecell 24 may include inlet unidirectional valve 36. Inlet unidirectionalvalve 36 may be configured to enable flow of fluid from reservoir 32 topressure cell 24 when suction is applied to pressure cell 24, whilepreventing backflow of liquid from pressure cell 24 toward reservoir 32.For example, inlet unidirectional valve 36 may be located at aninterface between inlet conduit 34 and pressure cell 24, as shown.Alternatively or in addition, inlet unidirectional valve 36 may belocated at an interface between reservoir 32 and inlet conduit 34, orelsewhere along inlet conduit 34. Alternatively or in addition, e.g.,when reservoir 32 is enclosed within handheld unit 12, one or more ofreservoir 32, plunger 16, or pressure cell 24 may be configured to sealoff flow between reservoir 32 and pressure cell 24 when pressure isapplied to pressure cell 24.

Since the only outlet from pressure cell 24 is orifice 27 of nozzle 26,the excess pressure may force the liquid out of pressure cell 24 viaorifice 27 in the form of a liquid micro-jet 30. The ejection of liquidmicro-jet 30 may relieve the excess pressure in pressure cell 24,restoring an equilibrium state where the pressure of the liquid iscountered by retaining forces (e.g., atmospheric pressure, adhesion,surface tension, or other forces at orifice 27).

After the distal displacement of actuation surface 18, impulse generator14 retracts actuation surface 18 in the proximal direction (away fromnozzle 26). The retraction displaces actuation surface 18 tosubstantially the original position of actuation surface 18 prior to thedistal displacement. When actuation surface 18 is retracted, one or morerestoration mechanisms similarly retract plunger 16 to its originalproximal position.

For example, the restoration mechanism may include a rigid bond ofplunger 16 to impulse generator 14, e.g., at actuation surface 18. Therigid bond may be formed as one piece with part of impulse generator 14(e.g., by casting, molding, or extruding plunger 16 and a part ofactuation surface 18 or of impulse generator 14 as a single piece, or bymachining a single piece to form them). The rigid bond may include abonding material (e.g., adhesive, glue, cement, epoxy, solder, or otherbonding material) a mechanical fastener (e.g., screw, clamp, or othermechanical fastener), magnetic attraction, or another rigid connection.Thus, the retraction of actuation surface 18 entails retraction of theconnected plunger 18. Such a rigid bond may enable precise control ofthe position of the plunger by controlling operation of impulsegenerator 14. (Such precise control may be especially advantageous in arepetitive needleless injection device 10 that does not include anoutflow unidirectional valve 28.)

Alternatively or in addition, the restoration mechanism may includeretraction mechanism 20. Retraction mechanism 20 may include a resilientelement such as a spring or deformable gasket, a magnet, or anotherelement, that exerts a restoring force on plunger 16 in the proximaldirection. Thus, after a pushing force of actuation surface 18 onproximal end 16 a of plunger 16 is released, possibly separatingactuation surface 18 from plunger 16, retraction mechanism 20 may pushplunger 16 in the proximal direction.

When a retraction mechanism 20 is used without a rigid connectionbetween actuation surface 18 and plunger 16, plunger 16 may separatefrom actuation surface 18 after exertion of a pushing force. Forexample, inertial of plunger 16 may cause proximal end 16 a to separatefrom actuation surface 18. Such separation may result in the amplitudeof the motion of plunger 16 being greater than that of the motion ofactuation surface 18. The increased amplitude of the displacement mayfurther increase the amount of liquid that is forced out of nozzle 26 byapplication of the pressure. Furthermore, the separation may increasethe rate of application of the excess pressure to pressure cell 24. Theincrease in rate of application of excess pressure may enable ejectionof liquid micro-jet 30 with increased velocity. The increased velocityof liquid micro-jet 30 may increase the depth of penetration of liquidmicro-jet 30 into the skin. The increased volume of liquid micro-jet 30may increase the resultant dose to the skin of a material that isdelivered by liquid micro-jet 30.

Retraction of plunger 16 by the restoration mechanism after expulsion ofliquid micro-jet 30 may create suction in pressure cell 24. The suctionmay draw liquid from reservoir 32 into pressure cell 24 via inletconduit 34 and inlet unidirectional valve 36. Alternatively or inaddition, when plunger 16 is retracted, liquid may flow from reservoir32 into pressure cell 24 via one or more openings that are opened byretraction of plunger 16.

Inflow of air via orifice 27 of nozzle 26 during application of suctionto pressure cell 24 may be prevented by outlet unidirectional valve 28that is configured to control flow through nozzle 26. Outletunidirectional valve 28 is configured to enable expulsion of a liquidmicro-jet 30 from pressure cell 24 through orifice 27 when excesspressure is applied to pressure cell 24. Outlet unidirectional valve 28is also configured to prevent inflow, e.g., of atmospheric air, throughorifice 27 of nozzle 26 into pressure cell 24 when suction is applied topressure cell 24. Thus, when suction is applied to pressure cell 24,inflow is enabled only from reservoir 32.

Alternatively or in addition to action of outlet unidirectional valve28, inflow of air through orifice 27 of nozzle 26 and into pressure cell24 during application of suction to pressure cell 24 may be prevented byadhesive forces and surface tension (or, collectively, capillary forces)that act on liquid in orifice 27. If the force of the applied suction onliquid in orifice 27 is less than the capillary forces, inflow of airthrough orifice 27 may be prevented. In this case, outlet unidirectionalvalve 28 may not be needed. For example, the capillary force may beexpressed as Hγ cos θ, where H is the circumference of the inner surfaceof orifice 27, γ is the surface tension of the liquid in orifice 27(e.g., in units of force per length), and θ is the fluid contact angleof the liquid in orifice 27 with the interior walls of orifice 27(dependent on adhesive forces between the liquid and the material of theinterior wall of orifice 27).

The flow of liquid from reservoir 32 into pressure cell 24 may replacethe volume of liquid that was ejected from pressure cell 24 in liquidmicro-jet 30. Replenishing the liquid in pressure cell 24 may restorepressure cell 24 to an equilibrium state.

A cycle of operation of repetitive needleless injection device 10includes operation of pushing plunger 16 to apply a pulse of excesspressure to pressure cell 24 to expel a liquid micro-jet 30, andretraction of plunger 16 to create a suction to replenish the supply ofliquid in pressure cell 24. The time required to complete this cycle isthe cycle time of repetitive needleless injection device 10. Forexample, the cycle time may be about 1 millisecond. In this case, themaximum repetition rate for a series of cycles is about 1000 hertz. Arepetition rate of about 1000 Hz may be sufficient to apply a dye at arate that is suitable for such applications as application of permanentmakeup or tattooing. Other repetition rates may be suitable for otherapplications (e.g., delivery or a drug or other therapeutic substance).

Reservoir 32 may include a liquid container vessel that is open toatmospheric pressure at opening 33. In this case, reservoir 32 mayinclude a stationary container that is connected to pressure cell 24 bya flexible inlet conduit 34. For example, a flexible inlet conduit 34may include a tube that is made of a flexible plastic or similarmaterial. Alternatively or in addition, inlet conduit 34 may beconstructed of a plurality of rigid tubes that are connected by flexiblejoints. The flexibility of inlet conduit 34 may enable free manipulationof handheld unit 12 while maintaining the fluid connection of pressurecell 24 to reservoir 32.

When reservoir 32 is open to atmospheric pressure and enclosed withinhandheld unit 12, opening 33 may be located on a side of handheld unit12 that is designated to face upward. For example, handheld unit 12 mayinclude a grip or other structure to facilitate maintaining anorientation of handheld unit 12 where opening 33 faces upward.Alternatively or in addition, opening 33 may be provided with baffles,unidirectional valves, or other structure to inhibit or prevent outwardspillage of liquid from reservoir 32 via opening 33. In some cases,opening 33 may be covered by a flexible membrane that transmits pressurewhile preventing spillage.

In some cases, reservoir 32 may be provided with a liquid level sensor38 to measure liquid level 31 of liquid in reservoir 32. For example,liquid level sensor 38 may be configured to generate a signal that isindicative of a sensed position (e.g., indicated by a sensed height,volume, pressure, electrical resistance, dielectric constant, radiationattenuation, refraction, heat conduction, or other quantity that may beindicative of liquid level 31) of liquid level 31. The generated signalmay be transmitted via sensor connection 35 to controller 40. Sensorconnection 35 may include an electric cable (e.g., a lightweight cablefor transmitting a low voltage signal) or a wireless connection.Alternatively or in addition, a counter or counting mechanism orfunction may be provided to count the number of pulses that were appliedby operation of impulse generator 14. If at least an approximate volumeof each ejected micro-jet 30 is known, a volume of the liquid thatremains in reservoir 32 may be estimated.

Controller 40 (e.g., circuitry of controller 40 or a processor 52 ofcontroller 40 operating in accordance with programmed instructions thatare stored on data storage device 58) may be configured to stopoperation of impulse generator 14 (e.g., by controlling operation oftriggering oscillator 54 or of actuator driver 56) when liquid level 31falls below a predetermined value. For example, the predetermined valuemay be a level that is sufficient to prevent air bubbles from forming ininlet conduit 34 or in pressure cell 24.

Alternatively or in addition, controller 40 may be configured togenerate an alert when liquid level 31 falls below a predeterminedthreshold level. For example, the generated alert may be output (e.g.,by producing a visible or audible indication using output device 44) toinform a user of repetitive needleless injection device 10 that liquidlevel 31 is low. The user may stop operation of impulse generator 14(e.g., by operating one or more user controls 42), may replenish thesupply of the liquid in reservoir 32, may replace reservoir 32, or mayperform another action in response to the generated alert.

Components of controller 40 may be external to handheld unit 12. Forexample, controller 40 may be connected to handheld unit 12 by aflexible wire or cable, or via a wireless connection. Alternatively orin addition, components of controller 40 may be enclosed within ormounted to handheld unit 12.

Controller 40 includes power supply 50. For example, power supply 50 mayinclude one or more batteries, photovoltaic cells, or anotherself-contained power source. Power supply 50 may include one or moretransformers or power converters to convert an electrical power signalfrom an external power source, e.g., from an electrical mains,generator, photovoltaic array, or another external power source to apower signal that is suitable for operation of one or more components ofrepetitive needleless injection device 10. In the case that componentsof controller 40 communicate wirelessly with components of handheld unit12, handheld unit 12 may be directly provided with a separate supply ofelectric power (or a component of power supply 50).

Controller 40 may include a processor 52. For example, processor 52 mayinclude one or more processing units, e.g. of one or more computers,that are configured to operate in accordance with programmedinstructions. Alternatively or in addition, processor 52 may includeanalog or digital circuitry that is configured to perform one or moreoperations, e.g., in a fixed manner in accordance with one or more inputparameter values that are selected by operation of user controls 42.

In some cases, a processor 52 in the form of a processing unit maycommunicate with data storage device 58. Data storage device 58 mayinclude one or more fixed or removable, volatile or nonvolatile memoryor data storage units. Data storage device 58 may include a computerreadable media. Data storage device 58 may be utilized to storeprogrammed instructions for operation of processor 52, data orparameters for use by processor 52 during operation, or results ofoperation of processor 52.

Processor 52 may be configured to receive signals from one or moresensors 57. For example, sensors 57 may include liquid level sensor 38.Sensors 57 may include one or more sensors that measure one or moreconditions that could affect operation of repetitive needlelessinjection device 10. For example, sensors 57 may be configured tomeasure one or more of a temperature (e.g., of the ambient atmosphere,of liquid in pressure cell 24, of the skin, or other temperature), abarometric pressure, relative humidity, a light or color sensor (e.g.,to monitor delivery of a dye to the skin), a flowmeter (e.g., in inletconduit 3 or elsewhere), a sensor to measure a property of a liquid inpressure cell 24 or in reservoir 32 (e.g., electrical or thermalconductivity, density, viscosity, pressure, color, or another property),or other relevant properties. Processor 52 may be configured to controloperation of repetitive needleless injection device 10 in accordancewith the sensed values. A processor 52 in the form of a processing unitmay be configured to interpret signals that are received from sensors 57to obtain a measured value, to store signals or measured values on datastorage device 58, or to utilize the measured values in controllingoperation of one or more components of repetitive needleless injectiondevice 10.

Processor 52 may be configured to operate triggering oscillator 54.Triggering oscillator 54 may include one or more clock circuits oroscillator devices. A frequency of operation of triggering oscillator 54may be adjustable, e.g., by operation of one or more user controls 42.Adjustment of an oscillation rate of triggering oscillator 54 maydetermine a repetition rate for operation of impulse generator 14 ofrepetitive needleless injection device 10.

User controls 42 may include one or more dials, pushbuttons, switches,levers, sliders, knobs, keys, touch screens, pointing devices,keyboards, keypads, microphones, or other devices that are operable by auser to control operation of controller 40 and of repetitive needlelessinjection device 10. For example, user controls 42 may be operated toadjust one or more parameters that determine a state of repetitiveneedleless injection device 10 (e.g., operate, standby, off, or anotherstate), delivered dose, a penetration depth of a delivered substanceinto the skin, a repetition rate, a threshold liquid level, or anotherparameter of operation of repetitive needleless injection device 10.

A current setting may be displayed or otherwise output, e.g., via outputdevice 44. Output device 44 may include one or more display screens,display panels, indicator lamps, speakers, printers, bells, buzzers,vibrators, or another device capable of producing visible, audible, ortactile output.

Processor 52 may be configured to operate actuator driver 56. Operationof actuator drive 56 may cause propulsion system 13 to generate a seriesof impulses that are applied to pressure cell 24. An impulse may becharacterized by a set of parameters that describe displacement ofpropulsion system 13 as a function of time. For example, the componentmay include one or more of actuation surface 18 and plunger 16 (e.g.,both when rigidly connected to one another).

FIG. 3 is a schematic pulse profile graph showing displacement as afunction of time of a component during a pulse of a propulsion system ofa repetitive needleless injection device, in accordance with anembodiment of the present invention.

Pulse profile graph 60 shows displacement as a function of time. Forexample, the displacement may represent one-dimensional displacement ofa part of plunger 16. Pulse profile 60 may be characterized by threeparameters, rise time 68, amplitude 66, and fall time 69. A displacementin the distal direction is represented in pulse profile graph 60 as apositive displacement.

In the example shown, pulse profile 60 includes a segment thatrepresents push phase 62. During push phase 62, a pressure pulse may begenerated by displacement of plunger 16. Push phase 62 is shown asnonlinear, approximately quadratic dependence of displacement on time.For example, push phase 62 in which displacement is a quadratic functionof time may represent generation of a pressure pulse by displacement ofplunger 16 with an approximately constant acceleration. A constantacceleration results from application of a constant force by mechanismactuator 14 to actuation surface 18 or to plunger 16. For example, anapproximately constant acceleration may be generated by applying alinearly increasing current to a piezoelectric actuator of impulsegenerator 14. A constant acceleration during push phase 62 may enableincreased efficiency of operation of propulsion system 13 over anotherform (e.g., linear, representing a constant velocity generated byapplying a constant current to a piezoelectric actuator of impulsegenerator 14) of push phase 61. Furthermore, the useful lifetime ofcomponents of propulsion system 13 may be increased when constantacceleration is applied.

Push phase 62 is characterized by a distal displacement of amplitude 66during rise time 68. For example, rise time 68 may be approximately 10microseconds, or another value.

The size of amplitude 66 may determine a volume of liquid micro-jet 30.For a constant cross sectional area of pressure cell 24, a volume ofliquid that is ejected in liquid micro-jet 30 during push phase 62 isproportional to amplitude 66. The volume of liquid in liquid micro-jet30 is thus controllable by controlling amplitude 66.

The rate at which liquid micro-jet 30 is ejected is proportional to risetime 68. The rate of ejection may determine a velocity of an ejectedliquid micro-jet 30. The velocity of liquid micro-jet 30 may, in turn,determine of depth of penetration into the skin of a substance that isdelivered by liquid micro-jet 30.

Pulse profile 60 includes a segment that represents retraction phase 64after ejection of liquid micro-jet 30. During retraction phase 64,plunger 16 is retracted to its start position (prior to commencement ofpush phase 62) during fall time 69. Fall time 69 may be determined byproperties of a restoration mechanism (e.g., of retraction mechanism 20)of propulsion system 13. During fall time 69, suction may be applied topressure cell 24. During fall time 64, the applied suction may causepressure cell 24 to replace the volume of liquid that was expelled inliquid micro-jet 30 with liquid from reservoir 32. Fall time 69 may besufficiently long so to avoid formation of bubbles (e.g., by cavitationor leakage) in pressure cell 24 or in inlet conduit 34. On the otherhand, fall time 69 may be sufficiently short so as to avoid excessiveelongation of the cycle time of propulsion system 13. For example, thelength fall time 69 may be about one millisecond, or another value.

User controls 42 may be operated to set one or more parameters ofoperation of repetitive needleless injection device 10. Typicaloperational parameters may include dose, penetration depth, repetitionrate, and liquid level. Additional parameters may be input by a useroperating user controls 42, may be stored on data storage device 58, maybe obtained from one or more sensors 57, or may be otherwise obtained.Such additional parameters may define a type of substance (or propertiesof the substance), a concentration of the substance in liquid contentsof pressure cell 24 and reservoir 32, characteristics of repetitiveneedleless injection device 10 or of handheld unit 12 (e.g., crosssectional area of pressure cell 24), or other parameters orcharacteristics of the substance, a liquid carrier of the substance, anambient environment, or of structure or operation of repetitiveneedleless injection device 10. Processor 52 may interpret the operationof user controls 42 to obtain the set parameters. Processor 52 may applythe parameters in operation of one or more components of repetitiveneedleless injection device 10.

For example, in order to deliver a specified dose of a substance at aparticular depth within the skin, processor 52 may control operation ofone or more of actuator driver 56 and triggering oscillator 54. Forexample, operating actuator driver 56 to control amplitude 66 of a pulsemay determine the volume of the liquid, or of a substance that iscarried by the liquid, that is ejected in each liquid micro-jet 30.Operating actuator driver 56 to control rise time 68 of a pulse maydetermine a velocity of expulsion of liquid micro-jet 30. The velocityof expulsion of liquid micro-jet 30 may affect the penetration depthinto the skin. Controlling a frequency of triggering oscillator 54 maycontrol a repetition rate of expulsion of liquid micro-jets 30. Therepetition rate may affect the total dose that is applied to an area ofskin when nozzle 26 is held at a single position on the skin or is movedslowly.

Parameters of design or operation of repetitive needleless injectiondevice 10 may be selected in order to satisfy various criteria. Forexample, volume of each micro-jet 30 may be selected in order to delivera substance to the skin at a particular dose rate. For example, thevolume may be no larger than 10 microliters. In some cases, the volumemay be less than 5 microliters. In some cases, the volume may be nolarger than 1.5 microliter.

A velocity of ejection of each micro-jet 30 may be selected in order todeliver a substance to a particular depth within the skin. In somecases, penetration depth may be proportional to the square of themicro-jet velocity. For example, the ejection velocity may be at least50 m/s. In some cases, ejection velocity may be at least 100 m/s.Different ranges of ejection velocities may be used for delivery of thesubstance to another type of surface other than human skin.

A set liquid level may determine or affect when processor 52 generatesan alert or modifies operation of repetitive needleless injection device10. For example, if liquid level sensor 38 senses a level that is belowa threshold value determined in accordance with a liquid levelparameter, an alert may be generated, actuator driver 56 or triggeringoscillator 54 may be controlled to reduce a dose or repetition rate, oractuator driver 56 or triggering oscillator 54 may be controlled to stopoperation of propulsion system 13.

A repetitive needleless injection device in accordance with anembodiment of the present invention may be compact. In a compactneedleless injection device, reservoir 32 is enclosed within handheldunit 12. Therefore, manipulation of handheld unit 12 may not be impededby any need to bend or avoid twisting an external inlet conduit 34. (Forexample, in some cases an external inlet conduit 34 may be sufficientlywide to provide an unimpeded flow of liquid from an external reservoir32 to pressure cell 24. The walls of the external inlet conduit 34 maybe sufficiently thick and stiff so as to prevent puncture and kinking.)

Some or all components of controller 40 may be external to handheld unit12. For example, a wired connection between handheld unit 12 andcontroller 40 may be sufficiently thin, lightweight, and flexible so asnot to noticeably impede manipulation of handheld unit 12.

FIG. 4A schematically illustrates a compact repetitive needlelessinjection device, in accordance with an embodiment of the presentinvention.

In compact needleless injection device 80, reservoir 32 is enclosedwithin handheld unit 12. For example, reservoir 32 may completely orpartially fill a space between propulsion system 13 (e.g., between oneor both of impulse generator 14 and plunger rod 82) and wall 78 ofhandheld unit 12. Opening 33 to reservoir 32 may enable refillingreservoir 32 and enables atmospheric pressure to propel liquid intopressure cell 24 when suction is applied to pressure cell 24. Opening 33may be located on a side of handheld unit 12 that is designed to faceupward. For example, handheld unit 12 may include a grip or otherguiding structure to facilitate maintaining an orientation of handheldunit 12 where opening 33 faces upward. Alternatively or in addition,opening 33 may be provided with one or more of a cover, baffle,unidirectional valve, or other structure configured to impede or preventoutward spillage of liquid from reservoir 32 via opening 33.

Inlet conduit 34 for connecting reservoir 32 with pressure cell 24 isinternal to plunger rod 82. The distal end of plunger rod 82 isconfigured to slide back and forth (distally and proximally) withindistal neck 85 of handheld unit 12. The outer diameter of plunger rod 82is sufficiently close to the inner diameter of distal neck 85 so as toprevent or impede flow of liquid between plunger rod 82 and distal neck85. Alternatively or in addition, sealing structure may be provided toprevent flow of liquid between plunger rod 82 and distal neck 85 whileenabling plunger rod 82 to slide within distal neck 85.

The distal end of distal neck 85, beyond the distal end of inlet conduit34, forms pressure cell 24.

Inlet conduit 34 is provided with conduit opening 83. Conduit opening 83is open to the interior of reservoir 32 to enable flow of liquid fromreservoir 32 into inlet conduit 34. Air outlet opening 39 is configuredto enable escape of any trapped air from inlet conduit 34 to the ambientatmosphere so as to prevent formation of bubbles in inlet conduit 34.Inlet unidirectional valve 36 the distal end of inlet conduit 34 isconfigured to enable outflow of liquid from inlet conduit 34 to pressurecell 24. Inlet unidirectional valve 36 is further configured to preventliquid in pressure cell 24 from flowing into inlet conduit 34. Thus,when plunger rod 82 is pushed distally, excess pressure may be appliedto liquid in pressure cell 24 so as to force a liquid micro-jet 30 to beexpelled from orifice 27 of nozzle 26. When plunger rod 82 is retractedproximally, capillary forces may limit or prevent inflow of air intopressure cell 24 via orifice 27. Therefore, the retraction of plungerrod 82 may cause a suction that opens inlet unidirectional valve 36.When inlet unidirectional valve 36 is open, liquid may flow fromreservoir 32 via inlet conduit 34 into pressure cell 24.

A diameter of orifice 27 may be selected in order to enable ejection ofa liquid micro-jet 30 having a diameter in a predetermined range. Forexample, a wide diameter may enable coverage of a large area within agiven period of time (e.g., when delivering a substance, such as apigment, to a general region). On the other hand, a narrow diameter mayenable drawing finer features on the skin (e.g., when delivering asubstance such as a pigment to a narrow region of skin, such as the edgeof an eyelid). For example, the useful diameter of orifice 27 for thisapplication may be no wider than 300 micrometers.

For example, impulse generator 14 may include a piezoelectric actuator.The piezoelectric actuator may or may not include a mechanicalamplifier. For example, in order to minimize the space occupied byimpulse generator 14, a piezoelectric actuator may not include apiezoelectric crystal without a mechanical amplifier.

In compact needleless injection device 80 as shown, plunger rod 82 maybe bonded to actuation surface 18 of impulse generator 14. Whenactuation surface 18 of impulse generator 14 is retracted in theproximal direction plunger rod 82 is also retracted.

FIG. 4B schematically illustrates a compact repetitive needlelessinjection device as in FIG. 4A with the addition of a unidirectionalvalve for impeding inflow of air.

In compact needleless injection device 81, nozzle cell 87 is separatedfrom pressure cell 24 by outflow unidirectional valve 28. Outflowunidirectional valve 28 enables liquid to flow distally outward frompressure cell 24 to nozzle cell 87 and to orifice 27 when excesspressure is applied to pressure cell 24 by plunger rod 82. On the otherhand, when plunger rod 82 is retracted to apply suction to pressure cell24, outflow unidirectional valve 28 prevents inflow of air throughorifice 27 and nozzle cell 87. Thus, the suction may draw liquid frominlet conduit 34 into pressure cell 24.

FIG. 5A schematically illustrates a compact repetitive needlelessinjection device as in FIG. 4A with the addition of a retainingmechanism.

Compact needleless injection device 90 includes a retraction mechanism20. Retraction mechanism 20 includes an elastic component 86 that iscompressed when plunger rod 82 is pushed in the distal direction byactuation surface 18 of impulse generator 14. For example, elasticcomponent 86 may include a spring or other resilient element that iscompressible between the proximal end of plunger rod 82 and anchor 84that is fixed to handheld unit 12. Plunger rod 82 may be retracted byre-expansion of elastic component 86 when actuation surface 18 isretracted. Thus, plunger rod 82 may be retracted without being bonded toactuation surface 18.

In some cases, whether or not the device includes a retaining mechanism,a resilient element, similar to elastic component 86, may becompressible between actuation surface 18 and anchor 84. Such aresilient element may preload a piezoelectric crystal of impulsegenerator 14. Such preloading may reduce mechanical shock to impulsegenerator 14. Reduction of shock may increase the usable lifetime of thepiezoelectric crystal.

FIG. 5B schematically illustrates a compact repetitive needlelessinjection device as in FIG. 5A with the addition of a unidirectionalvalve for impeding inflow of air.

Compact needleless injection device 91 includes retraction mechanism 20(similar to compact needleless injection device 90), together with anozzle cell 87 and outflow unidirectional valve 28 (similar to compactneedleless injection device 81).

In accordance with an embodiment of the present invention, aunidirectional valve, such as inlet unidirectional valve 36 or outflowunidirectional valve 28, may include a separable stopper on one side ofan aperture. When liquid flows through the aperture toward the side withthe separable stopper, the stopper separates from the aperture to enableflow through the aperture. When liquid flows toward the side of theaperture with the separable stopper, the stopper is pushed or draggedinto the aperture, thus blocking flow through the aperture. For example,the separable stopper may be represented by a ball whose diameter is atleast slightly larger than the diameter of the aperture.

FIGS. 6A-6E illustrate operation of unidirectional valves of arepetitive needleless injection device, in accordance with an embodimentof the present invention. For example, FIGS. 6A-6E may illustrateoperation of inlet unidirectional valve 36 and outflow unidirectionalvalve 28 of compact needleless injection device 81 or of compactneedleless injection device 91.

FIG. 6A schematically illustrates operation of a pair of unidirectionalvalves when no pressure is applied.

Inlet unidirectional valve 36 is closed, as represented by inlet valvestopper 92 in inlet valve aperture 95. Outflow unidirectional valve 28is closed, as represented by outlet valve stopper 94 in outlet valveaperture 93. Outflow unidirectional valve 28 includes restorationelement 96 for returning outlet valve stopper 94 to outlet valveaperture 93 when no forces are applied to outlet valve stopper 94.Restoration element 96 may limit opening of outflow unidirectional valve28 to enable a rapid response to a change in applied pressure. A rapidresponse may limit unwanted leakage or flow through outflowunidirectional valve 28 during transition from forward to backward flow.Restoration element 96 may include, for example, a spring or a magneticforce acting between the outlet valve stopper 94 and outlet valveaperture 93. (Although a similar restoration element may be provided forinlet unidirectional valve 36, for the sake of clarity none is shown.)

FIG. 6B schematically illustrates the unidirectional valves shown inFIG. 6A when a plunger rod is being pushed in the distal direction.

Plunger rod 82 is being pushed distally toward orifice 27. Inletunidirectional valve 36 remains closed while outlet valve stopper 94 ispushed away from outlet valve aperture 93 by excess pressure in pressurecell 24. Thus liquid may flow from pressure cell 24 through nozzle cell87 and out orifice 27 as a liquid micro-jet 30.

FIG. 6C schematically illustrates the unidirectional valves shown inFIG. 6B when the plunger rod has being pushed to its maximal extent.

Inlet unidirectional valve 36 remains closed while outflowunidirectional valve 28 remains open. Liquid micro-jet 30 has beencompletely expelled.

FIG. 6D schematically illustrates the unidirectional valves shown inFIG. 6C when the plunger rod is being retracted in the proximaldirection.

Outflow unidirectional valve 28 has been closed by action of restorationelement 96, separating pressure cell 24 from nozzle cell 87. Theretraction of inlet conduit 34 toward reservoir 32 cause liquid to flowfrom reservoir 32 via inlet conduit 34 into pressure cell 24. As plungerrod 82 is retracted, flow of liquid from reservoir 32 via inlet conduit34 into pressure cell 24 may separate inlet valve stopper 92 from inletvalve aperture 95. One or more additional or alternative forces, such assuction in pressure cell 24, inertia of inlet valve stopper 92, or dragforces between pressure cell 24 and liquid in pressure cell 24, may actto separate inlet valve stopper 92 from inlet valve aperture 95.

FIG. 6E schematically illustrates the unidirectional valves shown inFIG. 6D when the plunger rod has been fully retracted.

Outflow unidirectional valve 28 remains closed while inlet valve stopper92 remains separated from inlet valve aperture 95. Liquid has ceased toflow from reservoir 32 and inlet conduit 34 into pressure cell 24.

At this point, restoration forces (e.g., a resilient element or magneticforces) may act to return inlet valve stopper 92 to inlet valve aperture95. When inlet valve stopper 92 has returned to inlet valve aperture 95,the state shown in FIG. 6A is restored. Thus, compact needlelessinjection device 81 or compact needleless injection device 91 isprepared for ejection of another liquid micro-jet 30.

A method of operation of a repetitive needleless injection device 10, inaccordance with an embodiment of the present invention, may includefilling reservoir 32 with a liquid that is to be injected into asurface, such as a skin surface.

Orifice 27 of nozzle 26 of the device may be placed in proximity of thesurface into which the liquid is to be rejected. The distance betweenorifice 27 and the skin surface may be sufficiently small such that amicro-jet 30 that is ejected from orifice 27 impinges on the surfacewithout excessive interference (e.g., slowing, distortion, spreading, orscattering) by any intervening atmosphere. On the other hand, at least aminimal gap may be maintained between orifice 27 and the surface so asto prevent contamination of the nozzle 26 by materials (e.g., bacteriaor parasites) that are present on the surface. For example, the distancebetween orifice 27 and the surface may be no more than 5 mm. In somecases, the distance may be no greater than 3 mm.

Repetitive needleless injection device 10 may be operated to eject themicro-jets 30 liquid at a repetition rate, and each micro-jet 30 havinga volume, to deliver the liquid at a particular dose rate. Repetitiveneedleless injection device 10 may be operated to eject each micro-jet30 with a velocity of ejection so as to enable micro-jet 30 to penetratethe surface to a particular depth.

A piezoelectric crystal is more resistant to contraction forces than toexpansion forces. Therefore, it may be advantageous to configure aneedleless injection device so as to avoid internal expansion forces(e.g., following pushing of a plunger) that may disrupt the structure ofthe piezoelectric crystal.

FIG. 7A schematically illustrates an alternative propulsion mechanismfor the compact repetitive needleless injection device shown in FIG. 4A.

In alternative propulsion mechanism 100, hollow impulse generator 104,e.g., in the form of a hollow piezoelectric crystal, is enclosed insidemechanism housing 108. Hollow impulse generator 104 is such that plungerrod 82 may move in a longitudinal direction (distally or proximally)within longitudinal bore 105 of hollow impulse generator 104. Hollowimpulse generator 104 is configured to displace activation surface 18 inthe proximal direction when expanding. Propulsion spring 102 (or asimilar propulsion resilient element) is confined between activationsurface 18 and mechanism housing 108. Thus, proximal displacement ofactivation surface 18 compresses propulsion spring 102. Retaining spring106 (or a similar resilient element) is confined between plunger head 82a and mechanism housing 108.

FIG. 7B schematically illustrates a plunger retraction phase ofoperation of the alternative propulsion mechanism shown in FIG. 7A.

Hollow impulse generator 104 may be activated (e.g., by a controller) toto gradually expand to push activation surface 18 in the proximallydirection, compressing propulsion spring 102. Retaining spring 106expands to retract plunger rod 82, keeping plunger head 82 a pressedagainst activation surface 18.

FIG. 7C schematically illustrates an impulse generator contraction phaseof operation of the alternative propulsion mechanism shown in FIG. 7B.

After plunger rod 82 has been fully retracted, hollow impulse generator104 may be operated to rapidly contract (e.g., to its unexpanded lengthas indicated in FIG. 7A). The contraction of hollow impulse generator104 is sufficiently rapid such that hollow impulse generator 104 mayfully contract before re-expansion of propulsion spring 102 is able(e.g., has overcome inertia of plunger rod 82 and of propulsion spring102) to re-extend plunger rod 82 through an appreciable displacement.

FIG. 7D schematically illustrates a plunger extension phase of operationof the alternative propulsion mechanism shown in FIG. 7C.

After contraction of hollow impulse generator 104, propulsion spring 102expands to rapidly distally displace activation surface 18 to theproximal end of (contracted) hollow impulse generator 104. The rapiddistal displacement of activation surface 18 distally pushes on plungerhead 82 a to propel plunger rod 82. The impulse that is thus applied toplunger rod 82, and the inertia of the impelled plunger rod 82, mayfully extend plunger rod 82. The full extension of plunger rod 82 maycompress retaining spring 106. The full extension of plunger rod 82 maycause a micro-jet of liquid to be expelled via an opening at a distalend of a compact repetitive needleless injection device that includesalternative propulsion mechanism 100.

Finally, re-expansion of retaining spring 106 may retract plunger rod 82to its initial position (as shown in FIG. 7A)

FIG. 8 schematically illustrates a compact repetitive needlelessinjection device with a reservoir that is not coaxial with a propulsionsystem.

In non-coaxial compact needleless injection device 110, reservoir 32 islocated non-collinearly with propulsion mechanism 13.

Different embodiments are disclosed herein. Features of certainembodiments may be combined with features of other embodiments; thuscertain embodiments may be combinations of features of multipleembodiments. The foregoing description of the embodiments of theinvention has been presented for the purposes of illustration anddescription. It is not intended to be exhaustive or to limit theinvention to the precise form disclosed. It should be appreciated bypersons skilled in the art that many modifications, variations,substitutions, changes, and equivalents are possible in light of theabove teaching. It is, therefore, to be understood that the appendedclaims are intended to cover all such modifications and changes as fallwithin the true spirit of the invention.

While certain features of the invention have been illustrated anddescribed herein, many modifications, substitutions, changes, andequivalents will now occur to those of ordinary skill in the art. It is,therefore, to be understood that the appended claims are intended tocover all such modifications and changes as fall within the true spiritof the invention.

1. A device for repetitive needleless injection of a liquid into asurface, the device comprising: a handheld unit that includes at least acell that is fillable with the liquid, and a propulsion mechanismconfigured to apply a sequence of pressure pulses to the liquid, eachpulse of the sequence of pressure pulses to eject a micro-jet of theliquid from the cell via an orifice between the cell and an exterior ofthe handheld unit with a velocity that is sufficient to enable themicro-jet to penetrate into the surface; a reservoir that is connectedto the cell by a conduit to enable the liquid to flow from the reservoirto the cell to replace the liquid that is ejected in the micro-jet; acontroller that is configured to operate the propulsion mechanismrepeatedly so as to eject the sequence of the micro-jets; and aunidirectional valve to enable flow of the liquid from the reservoir tothe cell and to prevent backflow of the liquid from the cell to thereservoir, wherein the propulsion mechanism comprises: an impulsegenerator configured to displace an actuation surface to generate thepulse; a plunger configured to move linearly to transmit the pulse tothe cell, and a restoration mechanism to retract the plunger.
 2. Thedevice of claim 1, further comprising an outlet unidirectional valve,separating the orifice from the cell and configured to enable flow ofthe liquid from the cell to the orifice and to prevent inflow of airfrom the orifice to the cell.
 3. The device of claim 1, wherein theimpulse generator comprises a piezoelectric crystal.
 4. The device ofclaim 3, wherein the impulse generator comprises a mechanical amplifier.5. The device of claim 3, further comprising an actuator driver toactuate the impulse generator.
 6. The device of claim 5, wherein theactuator driver is configured to apply an increasing current to thepiezoelectric crystal.
 7. The device of claim 6, wherein the actuatordriver is configured to apply a linearly increasing current to thepiezoelectric crystal.
 8. The device of claim 5, wherein the actuatordriver is configured to apply a constant current to the piezoelectriccrystal.
 9. The device of claim 1, wherein the restoration mechanismcomprises a rigid bond between the plunger and the actuation surface.10. The device of claim 1, wherein the restoration mechanism comprises aretraction mechanism.
 11. The device of claim 10, wherein the retractionmechanism comprises an element for exerting a restoring force on theplunger.
 12. The device of claim 11, wherein the element for exertingthe restoration force may be selected from the group consisting of: aresilient element, a spring, a deformable gasket and a magnet.
 13. Thedevice of claim 1, wherein the controller is configured to controloperation of the propulsion mechanism so as to control one or both of anamplitude of the pulse and a rise time of the pulse.
 14. The device ofclaim 13, wherein the controller is configured to control said one orboth of an amplitude of the pulse and a rise time of the pulse inaccordance with an indicated dose or a penetration depth.
 15. The deviceof claim 1, wherein the controller is configured to control operation ofthe propulsion mechanism so as to control a repetition rate forgeneration of the pulses.
 16. The device of claim 1, wherein thereservoir comprises a liquid level sensor to sense a level of the liquidin the reservoir and the controller is configured to stop operation ofthe propulsion mechanism when the sensed liquid level is below athreshold level.
 17. The device of claim 1, wherein the reservoir andthe conduit are enclosed within the handheld unit.